Streptolysin O enhances keratinocyte migration and proliferation and promotes skin organ culture wound healing in vitro

ML-05, a modified form of the hemolytic and cytotoxic bacterial toxin, streptolysin O, is currently being investigated as a treatment for collagen-related disorders such as scleroderma and fibrosis. Furthermore, ML-05 may be effective in promoting wound healing and alleviating the formation of hypertrophic scars and keloids. To investigate the effects of ML-05 on wound-healing processes, in vitro wound-healing scratch assays (using human primary epidermal keratinocytes and dermal fibroblasts) and a human skin organ culture wound model were utilized. ML-05 markedly enhanced keratinocyte migration and proliferation in wound scratch assays. ML-05 did not affect either proliferation or migration of dermal fibroblasts, indicating that ML-05's effects on cell migration/proliferation may be keratinocyte-specific. ML-05 was tested in a dose-dependent manner in a skin organ culture wound model using two different application methods: Through the culture media (dermal exposure) or direct topical treatment of the wound surface. ML-05 was found to accelerate wound healing as measured by reepithelialization, particularly after topical application. Therefore, ML-05 may have potential as a wound-healing agent that promotes reepithelialization through stimulation of keratinocyte migration and proliferation.     

Clinical application of growth factors and cytokines in wound healing

Wound healing is a complex and dynamic biological process that involves the coordinated efforts of multiple cell types and is executed and regulated by numerous growth factors and cytokines. There has been a drive in the past two decades to study the therapeutic effects of various growth factors in the clinical management of nonhealing wounds (e.g., pressure ulcers, chronic venous ulcers, diabetic foot ulcers). For this review, we conducted an online search of Medline/PubMed and critically analyzed the literature regarding the role of growth factors and cytokines in the management of these wounds. We focused on currently approved therapies, emerging therapies, and future research possibilities. In this review, we discuss four growth factors and cytokines currently being used on and off label for the healing of wounds. These include granulocyte‐macrophage colony‐stimulating factor, platelet‐derived growth factor, vascular endothelial growth factor, and basic fibroblast growth factor. While the clinical results of using growth factors and cytokines are encouraging, many studies involved a small sample size and are disparate in measured endpoints. Therefore, further research is required to provide definitive evidence of efficacy.     

Defining outcomes for β‐cell replacement therapy in the treatment of diabetes: a consensus report on the Igls criteria from the IPITA/EPITA opinion leaders workshop

β‐cell replacement therapy, available currently as pancreas or islet transplantation, has developed without a clear definition of graft functional and clinical outcomes. The International Pancreas & Islet Transplant Association (IPITA) and European Pancreas & Islet Transplantation Association (EPITA) held a workshop to develop consensus for an IPITA/EPITA Statement on the definition of function and failure of current and future forms of β‐cell replacement therapy. There was consensus that β‐cell replacement therapy could be considered as a treatment for β‐cell failure, regardless of etiology and without requiring undetectable C‐peptide, accompanied by glycemic instability with either problematic hypoglycemia or hyperglycemia. Glycemic control should be assessed at a minimum by glycated hemoglobin (HbA_1c) and the occurrence of severe hypoglycemia. Optimal β‐cell graft function is defined by near‐normal glycemic control [HbA_1c ≤ 6.5% (48 mmol/mol)] without severe hypoglycemia or requirement for insulin or other antihyperglycemic therapy, and with an increase over pretransplant measurement of C‐peptide. Good β‐cell graft function requires HbA_1c < 7.0% (53 mmol/mol) without severe hypoglycemia and with a significant (>50%) reduction in insulin requirements and restoration of clinically significant C‐peptide production. Marginal β‐cell graft function is defined by failure to achieve HbA_1c < 7.0% (53 mmol/mol), the occurrence of any severe hypoglycemia, or less than 50% reduction in insulin requirements when there is restoration of clinically significant C‐peptide production documented by improvement in hypoglycemia awareness/severity, or glycemic variability/lability. A failed β‐cell graft is defined by the absence of any evidence for clinically significant C‐peptide production. Optimal and good functional outcomes are considered successful clinical outcomes.     

Antihistamine Responsive Cluster Headache in a Teenaged Girl

Episodic cluster headache is a well-recognized entity usually starting in the second decade of life. Uncommonly, the first typical symptoms may present in the first decade of life, but are rarely recognized as such during childhood. We report a 12-year-old girl who presented with a 1-year history of bouts of right-sided hemicrania with ipsilateral, clearly demarcated, redness and itching of the skin of the face, lasting from 15 minutes to 2 hours per day. The episodes recurred up to several times daily for a few days and were followed by remissions lasting up to 2 months. Thorough investigations failed to prove any definite cause. Antihistamine prophylaxis, first with astemizole and then with Ioratadine, proved to be very effective. During the follow-up period of more than 3 years, such a prophylactic regimen provided excellent relief, with only two relapses due to noncompliance. We suggest that in a sequential treatment trial for cluster headache during childhood, antihestamines should have their place, especially in those cases where clinical evidence may suggest histamine involvement.     

Essential oils rich in monoterpenes are unsuitable as additives to boar semen extender

Despite the development of efficient boar semen extenders, there is still room for improvement of new formulas using new molecules that could increase fertilisation outcomes and substitute cryoprotectants and antibiotics. The goal of this work was to evaluate if the essential oils from the leaves of Myrrhinium atropurpureum and Cymbopogon citratus are suitable as additives in boar semen extender. The major compounds found in the essential oils from M. atropurpureum were 1,8‐cineole (37.37%) and terpinolene (19.18%); and geranial (49.8%) and neral (33.24%) in essential oil of C. citratus. The addition of 1% and 0.1% of both essential oils to extended semen had immediate spermicidal effects (p < 0.05). Lower concentrations were tested and no cytotoxic effect was observed when M. atropurpureum essential oil was added at 0.001%. Differently, essential oil from C. citratus reduced sperm motility, membrane functionality and integrity and mitochondrial membrane potential even in concentrations as low as 0.001%. Also, addition of essential oils in low concentrations had no inhibitory effect against Escherichia coli and Pseudomonas aeruginosa growth. We conclude that the essential oils from C. citratus and M. atropurpureum, rich in monoterpenes, are cytotoxic to swine spermatozoa, therefore unsuitable as semen extender additives.     

Properties of flavonoids influencing the binding to bilitranslocase investigated by neural network modelling

Bilitranslocase is a plasma membrane carrier firstly identified on the sinusoidal (vascular) domain of liver cells and later on also in the gastric epithelium. It transports diverse organic anions, such as bilirubin, some phthaleins and many dietary anthocyanins, suggesting that it could play a role both in the absorption of flavonoids from dietary sources and in their hepatic metabolism. This work was aimed at characterising the interaction of bilitranslocase with flavonols, a flavonoid sub-class. The results obtained show that, contrary to anthocyanins, flavonol glycosides do not interact with the carrier, whereas just some of the corresponding aglycones act as relatively poor ligands to bilitranslocase. These data point to a clear-cut discrimination between anthocyanins and flavonols occurring at the level of the bilitranslocase transport site. A quantitative structure-activity relationship based on counter propagation artificial neural network modelling was undertaken in order to shed light on the nature of flavonoid interaction with bilitranslocase. It was found that binding relies on the ability to establish hydrogen bonds, ruling out the involvement of charge interactions. This requisite might be at the basis of the discrimination between anthocyanins and flavonols by bilitranslocase and could lie behind some aspects of the distinct pharmacokinetic properties of anthocyanins and flavonols in mammals.     

The role of surgical debridement in healing of diabetic foot ulcers

A critical question in the treatment of chronic wounds is whether and when debridement is needed. The three most common chronic wounds are the diabetic foot ulcer (DFU), the venous leg ulcer, and the pressure or decubitus ulcer. Surgical debridement, aimed at removing necrotic, devitalized wound bed and wound edge tissue that inhibits healing, is a longstanding standard of care for the treatment of chronic, nonhealing wounds. Debridement encourages healing by converting a chronic nonhealing wound environment into a more responsive acute healing environment. While the rationale for debridement seems logical, the evidence to support its use in enhancing healing is scarce. Currently, there is more evidence in the literature for debridement for DFUs than for venous ulcers and pressure ulcers; however, the studies on which clinicians have based their rationale for debridement in DFUs possess methodologic flaws, small sample sizes, and bias. Thus, further studies are needed to develop clinical evidence for its inclusion in treatment protocols for chronic wounds. Here, the authors review the scientific evidence for debridement of DFUs, the rationale for debridement of DFUs, and the insufficient data supporting debridement for venous ulcers and pressure ulcers.     

Long lasting remission by rituximab in a patient with primary cold agglutinin autoimmune haemolytic anaemia

A 76-year-old female patient with cold agglutinin autoimmune haemolytic anaemia (CAHA) is presented. The haemolysis worsened during infection. Earlier, the patient underwent an unsuccessful treatment with steroids, chlorambucil , folic acid and heated erythrocyte transfusion. We treated her with monoclonal anti-CD20 antibody Rituximab (RTX) weekly for four consecutive weeks. After three cycles, the signs of haemolysis slowly disappeared and haemoglobin completely normalized. We continued with the maintenance treatment with RTX every third month for 2 years. The patient is in complete remission. This case report emphasizes the importance of the use of RTX as a therapy for immune cytopenia. Patients with CAHA usually fail to respond to standard treatment. Since CAHA is a very rare condition, only some case reports and 2 studies reported on the positive effects of RTX. Although expensive, RTX has many advantages, such as quick and long-term efficiency and only a few side effects.